Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase

Yuichi Sekine, Satoshi Tsuji, Osamu Ikeda, Kenji Sugiyma, Kenji Oritani, Kazuya Shimoda, Ryuta Muromoto, Norihiko Ohbayashi, Akihiko Yoshimura, Tadashi Matsuda

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36 Citations (Scopus)

Abstract

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that contains pleckstrin homology- and Src homology 2-like domains as well as a YXXQ motif in its C-terminal region. Our previous studies demonstrated that STAP-2 binds to STAT3 and STAT5, and regulates their signaling pathways. In the present study, we find that STAP-2-deficient splenocytes or T cells exhibit enhanced cell adhesion to fibronectin after PMA treatment, and that STAP-2-deficient T cells contain the increased protein contents of focal adhesion kinase (FAK). Furthermore, overexpression of STAP-2 induces a dramatic decrease in the protein contents of FAK and integrin-mediated T cell adhesion to fibronectin in Jurkat T cells via the degradation of FAK. Regarding the mechanism for this effect, we found that STAP-2 associates with FAK and enhances its degradation, proteasome inhibitors block FAK degradation, and STAP-2 recruits an endogenous E3 ubiquitin ligase, Cbl, to FAK. These results reveal a novel regulation mechanism for integrin-mediated signaling in T cells via STAP-2, which directly interacts with and degrades FAK.

Original languageEnglish
Pages (from-to)2397-2407
Number of pages11
JournalJournal of Immunology
Volume179
Issue number4
DOIs
Publication statusPublished - 2007 Aug 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sekine, Y., Tsuji, S., Ikeda, O., Sugiyma, K., Oritani, K., Shimoda, K., Muromoto, R., Ohbayashi, N., Yoshimura, A., & Matsuda, T. (2007). Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase. Journal of Immunology, 179(4), 2397-2407. https://doi.org/10.4049/jimmunol.179.4.2397